With an estimated 33 million persons living with HIV-1, 2.1 millions deaths from AIDS in 2007, and 2.5 million new HIV-1 infections per year worldwide, the global impact of HIV-1 and AIDS continues to be overwhelming, despite advances in treatment of chronic HIV-1 infection and improved access to treatment in developing countries\ Even in the United States, whose epidemic is dwarfed by that in developing countries, HIV-1 infection has had major health and social impacts: an estimated 1.3 million persons were living with HIV-1 infection and 56,000 people were newly infected in 2007[1,2]. Virologic and immunologic data germane to development of biomedical preventative strategies such as vaccines is critically important. 3.1 Viral Correlates of Sexual Transmission of HIV-1. The strongest viral correlate of sexual transmission has been plasma HiV-1 RNA levels[3,4]. HIV RNA levels in plasma and genital secretions correiate[5,6] and seminal plasma have been correlated with transmission probability[7,8]. More recent data suggest that distinct viral variants may be enriched in genital secretions compared with blood plasma although data are conflicting [9-12]. Many studies of sexual transmission over the years have shown that infections with HIV-1 subtype B typically (current estimates are 70-80[13,14,15]) originate from single virus founders. However, data from heterosexual African women and men who had recently acquired HIV-1 subtypes A or D demonstrated that 20 of 32 women had multiple viral variants whereas all 10 of the men studied had a single variant^^. These data suggest that sex of the Infected individual or viral subtype might modify the characteristics of the transmitted virus. Other studies have suggested that other viral characteristics such as such as env glycoprotein N-llnked glycosylation or env lengths may impact transmissibility^^'^^, though again this may be subtype-specific[2021] (see Projects 1 and 3 for more detailed discussions).